{"doi":"10.1002/eji.202350559","title":"Multifunctional cytokine production marks influenza A virus‐specific CD4 T cells with high expression of survival molecules","abstract":"Abstract Cytokine production by memory T cells is a key mechanism of T cell mediated protection. However, we have limited understanding of the persistence of cytokine producing T cells during memory cell maintenance and secondary responses. We interrogated antigen‐specific CD4 T cells using a mouse influenza A virus infection model. Although CD4 T cells detected using MHCII tetramers declined in lymphoid and non‐lymphoid organs, we found similar numbers of cytokine + CD4 T cells at days 9 and 30 in the lymphoid organs. CD4 T cells with the capacity to produce cytokines expressed higher levels of pro‐survival molecules, CD127 and Bcl2, than non‐cytokine + cells. Transcriptomic analysis revealed a heterogeneous population of memory CD4 T cells with three clusters of cytokine + cells. These clusters match flow cytometry data and reveal an enhanced survival signature in cells capable of producing multiple cytokines. Following re‐infection, multifunctional T cells expressed low levels of the proliferation marker, Ki67, whereas cells that only produce the anti‐viral cytokine, interferon‐γ, were more likely to be Ki67 + . Despite this, multifunctional memory T cells formed a substantial fraction of the secondary memory pool. Together these data indicate that survival rather than proliferation may dictate which populations persist within the memory pool.","journal":"European Journal of Immunology","year":2023,"id":370270,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1129413,"name":"Jonathan Noonan","orcid":"0000-0001-9173-0903","position":1,"is_corresponding":false},{"id":480889,"name":"Kerrie E Hargrave","orcid":"0000-0001-6015-4616","position":2,"is_corresponding":false},{"id":731648,"name":"Elizabeth Chimbayo","orcid":"0000-0001-6232-6514","position":3,"is_corresponding":false},{"id":1129414,"name":"Zhiling Cheng","orcid":"0000-0001-6026-2887","position":4,"is_corresponding":false},{"id":1083769,"name":"Thomas Purnell","orcid":"0000-0002-9551-7947","position":5,"is_corresponding":false},{"id":1129415,"name":"Mark R. Jackson","orcid":"0000-0003-3843-2995","position":6,"is_corresponding":false},{"id":251348,"name":"Nicholas Borcherding","orcid":"0000-0003-1427-6342","position":7,"is_corresponding":false},{"id":457701,"name":"Megan K. L. MacLeod","orcid":"0000-0003-1843-8580","position":8,"is_corresponding":false},{"id":1129412,"name":"Lotus M Westerhof","orcid":"0000-0002-6808-9908","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T01:15:37.094100Z","pmid":"37490492","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}